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NCRI Sarcoma

Clinical Studies Group

Annual Report 2017-18

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NCRI Sarcoma CSG

Annual Report 2017-18

1. Top 3 achievements in the reporting year

Achievement 1

Achieving funding for ICONIC from Bone Cancer Research Trust (BCRT): Improving outcome

through Collaboration in OsteosarComa

Funding: Details are as follows:

• Dr Sandra Strauss (Chief Investigator), Professor Jeremy Whelan, Professor Bernadette

Brennan, Mr Craig Gerrand, Flanagan A et al,

• Funder: BCRT

• Sponsor: University College London Cancer Trials Centre (UCL CTC)

• Sum: £449,631.79

Trial summary: The purpose of this programme is to deliver a step-change in our approach to

seeking better treatments for osteosarcoma (OS) by establishing a clinically annotated cohort

of newly diagnosed patients with OS with longitudinal collection of bio-specimens to serve as a

platform for biological studies.

Achievement 2

Opening the first portfolio study on chondrosarcoma, which is now open in four of the five

primary bone sarcoma centres. Does circulating DNA predict the grade and disease burden of

chondrosarcoma? The nationwide collaboration study details are: -

• Investigators: Professor Adrienne Flanagan (CI), Professor Lee Jeys & Mr Craig Gerrand

• Funder: BCRT

• Sum: £69,963

• Sponsor: Royal National Orthopaedic Hospital, London

• Design: Observational study with biological arm

• Trial Period: 13/10/2017 – 01/11/2020

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• Recruitment: 29/130 patients, on target

Trial summary. This study looks at circulating IDH1 mutations in the blood of patients with

chondrosarcoma, and aims to correlate with the final pathological diagnosis. It also proves the

principal that multicentre collaboration is feasible in this condition and is a platform on which

to develop further studies.

Achievement 3

Achieving funding for FaR-RMS: A multi-arm-multistage study for children and adults with

localised and metastatic Frontline and Relapsed Rhabdomyosarcoma.

Funding: Details are as follows:

• Dr Meriel Jenney (CI), Dr Julia Chisholm, Dr Henry Mandeville., Professor Keith Wheatley.,

Merks H et al.; CRUK/17/011 FaR-RMS: A multi-arm-multistage study for children and

adults with localised and metastatic Frontline and Relapsed RhabdoMyoSarcoma. January

2018 - December 2028

• Funder: Cancer Research UK (CRUK)

• Sum: £2,330,159.53

Trial summary: The FaR-RMS Study is an overarching clinical trial that explores several aspects

of treatment for RMS, both for patients newly diagnosed with the disease and also at the time

of relapse. It is open to patients of all ages (children, teenagers and young adults (TYA) and

adults) across Europe who are newly diagnosed with RMS or in whom the disease recurs.

2. Structure of the Group

The membership of the Sarcoma CSG has evolved since 2016 and the Group is extremely

welcoming, collegiate and engaging. Unlike many CSGs, the number of research active clinicians

working in the field of sarcoma is limited and thus the number of suitable members is also

limited, resulting in several members sitting on the committee for many years. This brings with it

great experience of opening and running large trials, however, encouraging younger members of

the community to develop trials for the future is also fundamental for the longer-term success of

the CSG. The Group remains dynamic and productive, being on course to deliver the objectives

set after the strategy day held in 2016.

Dr Helen Hatcher, Professor Jeremy Whelan, Miss Ray Davis and Dr Alexander Lee rotated off the

group and were thanked for their hard work and contributions made whilst members of the Group.

This year the CSG welcomed new members: Professor Sue Burchill, Dr Louise Carter and Professor

Luc Bidaut.

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3. CSG & Subgroup strategies

Main CSG

Increase the number of trials available for sarcoma patients in the UK

This reporting year the portfolio has seen the funding or opening of several studies developed

with or by the CSG which will increase the number of trials open to sarcoma patients.

Important studies have been opened in Chondrosarcoma and Chordoma, both of which have

started with good initial recruitment. Euro-Ewings remains an important large randomised

international study with 179 patients recruited within the UK. The recent funding of the ICONIC

study means that when this opens, there will be a study for all major types of bone cancer for

patients, which is a massive achievement. There are also a number of new studies for

relapsed bone sarcoma.

The major advance has been the initialisation of phase II of Sarcoma Assessment Measure

(SAM), a large study for all sarcoma patients which plans to recruit 1000 patients. There have

been several new phase I/II studies open for patients with soft tissue sarcoma (STS) open this

year, including for the most common STS subtype, undifferentiated pleomorphic sarcoma and

several studies for advanced disease in STS. An industry sponsored phase III study is also

available for patients with advanced disease.

Develop new trials with both interventional and non-interventional arms and allow as many

patients with sarcoma to enter data into studies

The CSG has worked hard to develop three major bone studies with observational and

translational arms in osteosarcoma, chondrosarcoma and chordoma, all of which have been

funded and 2 are open. FaR-RMS and EpSSG NRSTS 2018 studies will have both

interventional and translational arms for TYA and paediatric patients. SARC MET trial is still in

development by the Lung Mets Working Party and plans to have both interventional and non-

interventional elements in an attempt to make the study available to all patients with

metastatic STS.

Increase studies in bone sarcoma

The Bone and YOSS Subgroups, together with the main CSG have done an excellent job in:

• Obtaining significant funding for the ICONIC study for osteosarcoma, in the lack of a

successor study to EURAMOS. A study which will aim to recruit all patients in UK with

Osteosarcoma and has a strong translational element.

• Opening the study ‘Does circulating DNA predict the grade and disease burden of

chondrosarcoma? A nationwide collaboration study’. The first portfolio study in

chondrosarcoma with a strong translational arm and encourages the 5 bone sarcoma

MDTs in England to collaborate and share tissue. This study will also recruit patients with

benign enchondromas to study the link between the pre-malignant condition and

chondrosarcoma.

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• Opening the Guiding Chordoma Treatment Through Molecular Profile which again has a

large translational arm and is open to all patients irrespective of stage in this rare

condition.

• Continuing to support the multiple studies in Ewing’s sarcoma, including the large

international randomised studies, EUROEWING and rEEcur. There are also some stand-

alone translational studies open for Ewing’s sarcoma.

The three new studies mean that there is now a study open for every major bone sarcoma

subtype and the SAM study is open for all bone sarcomas.

Further develop the Sarcoma CSG portfolio

The CSG is in the process of developing a Soft Tissue Sarcoma Subgroup, with Dr Aisha Miah

as Chair and good engagement from both within and without the CSG. The CSG is confident

this Subgroup will develop further over-arching trials in STS which are needed. The Lung Mets

Working Party is developing SARC-MET study which has been under extensive discussion

within the CSG, and should be submitted for funding in 2018.

A key strategic aim for the CSG following the Strategy Day was to develop studies which gave

opportunity for the whole sarcoma community to take part in trials the opening of the new

bone sarcoma trials and Sarcoma Assessment Measure trial have given this opportunity. The

opportunity to further develop STS trials through a new STS Subgroup will also enhance this

aim. The CSG was also cognisant to ensure new trials had strong translational arms and again

this has been the case. Another priority was to engage with the limited number of sarcoma

MDTs in the UK to develop a sarcoma research network, the ICONIC, Chondrosarcoma and

Chordoma trials deliberately have collaboration at their heart and often study title to achieve

this goal.

The CSG has changed the structure of the main meetings to give ample time for trial

development and updates. The Group has invited investigators of studies developed outside

the main CSG to present their proposals prior to submission to the CSG for feedback,

awareness and endorsement of the CSG. The CSG has also regularly invited funder

representatives from CRUK, Sarcoma UK and BCRT to attend meetings to try to harmonise

future applications with research calls, to maximise the chance of successful application and

allow a two-way dialogue with funders.

Raise awareness and profile

The CSG has a regular section at the British Sarcoma Group (BSG) to disseminate the new trial

ideas and studies which are opening, this also allows the CSG to engage with the sarcoma

community to uncover areas of unmet research need from the sarcoma community. The

interaction between the NIHR Sub-Specialty Leads (SSLs) and the CSG has been variable and

sometimes problematic. Highlights from the CSG meeting are disseminated to the SSLs and

there have been attempts to hold meetings with the SSLs and invite them to the main CSG

meeting, however, this has been with limited success. One of the main issues is that the

Sarcoma SSL is not always a sarcoma clinician in some CRNs and that a significant number of

Sarcoma SSL positions remain unfilled. The CSG requires engagement with the SSLs to ensure

adequate uptake of new trials on the portfolio, however, due to centralisation of care, the

number of units recruiting to portfolio studies is limited. The CSG therefore encourages the

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chief investigation or trial management group of portfolio studies to liaise directly with units

that are recruiting to studies; this has been successful so far.

The early results of trials have been presented at important scientific meetings such as the

American Society of Clinical Oncology (ASCO), Connective Tissue Oncology Society (CTOS), NCRI

and BSG. The CSG continues to publish the results of trials in high impact journals.

Develop trials in key research priority areas

The CSG is proud that of the research ideas developed at the Strategy Day, new trials have

been funded or opened in all the major areas which were felt to be key. The more problematic

areas of surgical trials, follow up studies and more STS trials require further work. The CSG has

tried to embed surgical questions into larger studies, such as ICONIC, where surgical margin

validation in the context of response to chemotherapy is a major part of the study, together

with radiological estimation of response to chemotherapy. The Group is aware of areas which

require development and hope that SARC-MET will obtain funding in the near future to fulfil

another key research area.

A number of small and medium size trials are currently open on the portfolio, with 5 industry

trials undergoing adoption/set up currently and the CSG has engaged with industry, recently

the AZ Alliance, to identify possible novel agents for soft tissue sarcoma, with 2 trial proposals

presented at the last meeting in May.

Strengthen UK wide and international working

Given the size of the national and international community the CSG has always benefitted from

close links with national and international organisations. This is clearly seen within the studies

in the portfolio and in development. The CSG has representatives on key research

organisations such as European Organisation for Research and Treatment of Cancer (EORTC),

Children’s Oncology Group (COG), Scandinavian Sarcoma Group (SSG), European paediatric

Soft tissue sarcoma Study Group (EpSSG), Euro Ewing Consortium (EEC), IOC and Chordoma

Foundation. This remains a strong and important priority for the CSG.

The CSG also regularly interacts with other NCRI groups with members sitting on Consumer

Forum, SPED Advisory Group and Teenage & Young Adult (TYA) & Germ Cell Tumours (GCT)

CSG and Dr Sandra Strauss is the Sarcoma Site Specific Clinical Reference Group (SSCRG)

Chair for National Cancer Registration and Analysis Service (NCRAS) for sarcoma. The CSG has

benefitted from interaction with Children’s Cancer & Leukaemia CSG, Gynaecological Cancer

CSG, Primary Care CSG, Psychosocial Oncology & Survivorship CSG, Supportive & Palliative

Care CSG and TYA & GCT CSG either in the main meetings or via interaction with subgroups.

The CSG has excellent links with the sarcoma community within the UK. The CSG annually

presents current research projects and trials ideas at the annual BSG meeting, which is a

multidisciplinary group of clinicians and consumers, to gain feedback for trial ideas, publicise

trials and their results. The CSG has presented trial results at ASCO, NCRI Conference and

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CTOS. Members of the CSG also regularly contribute to consumer conferences for Sarcoma

UK, BCRT and Sarcoma Patients EuroNet (SPAEN).

CSG structure and function

The current core membership includes 22 members from a variety of backgrounds relevant to

sarcoma research. The group currently consists of 3 clinical oncologists, 4 medical oncologists,

3 orthopaedic oncology surgeons, 2 paediatric oncologists, 2 consumer representatives, 2

trainee representatives (a clinical oncologist and clinical research fellow – both with a strong

background in basic science research), a medical physicist (with expertise in imaging), a

pathologist, a sarcoma specialist nurse, a sarcoma scientist, a statistician and a trial co-

ordinator.

The strength of the CSG lies in the diversity of its membership; with several members holding

academic positions undertaking basic science research, as well as clinical positions, thus

giving expertise for both clinical and biological research. Several of the members have been

involved in devising, gaining funding, running and concluding large national and international

trials, which serves as a great inspiration and an invaluable resource for the group.

Representatives of two of the main charitable funders of sarcoma research, Sarcoma UK and

BCRT, attend the meeting, which provides valuable feedback to the members and helps the

charities consider areas of unmet research needs. The CSG regularly debate the skills within

the group and areas which could be strengthened. The Chair has pro-actively approached

several individuals with skills in areas under-represented and encouraged them to apply for to

join the CSG or subgroups.

Patient and Public Involvement and Impact

The consumer involvement within the CSG remains good with Mr Michael Maguire being the

current the consumer representative, as Miss Ray Davies had to withdraw from the CSG due to

a career move abroad. Former consumer member Mr Roger Wilson CBE remains a scientific

advisor to the CSG and former consumer member Mr Robert Wensley remains a member of

the NCRI Consumer Forum. Both Roger and Michael have been involved in the development of

studies with the last year, as well as being active in the NCRI Consumers Forum ‘Dragons Den’.

The CSG is aware that having at least one consumer who is a sarcoma patient rather than a

care giver would be advantageous. The CSG has worked with Sarcoma UK and BCRT to identify

patients active in their organisations that may be suitable to join the CSG and subgroups. The

CSG is hopeful for a positive response to the current advert for consumer members.

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Bone Tumour Subgroup (Chair, Mr Craig Gerrand)

Develop studies in bone sarcoma through wide engagement, including involvement with

charitable partners and national collaboration

By widening participation in the Subgroup, with the support of BCRT, we have been able to

increase engagement and support the development of new studies. This approach of opening

the doors has been successful and means there is a wide range of members with a breadth of

experience that covers the areas necessary for translational medicine, drug trials and TYA

trials. We have had surgical and pathology engagement to good effect leading in particular to a

new study in chondrosarcoma which has recently opened. The Subgroup has also recently

developed the ICONIC study for osteosarcoma, in the absence of an international follow on

study to EURAMOS. This study aims to recruit all patients with osteosarcoma in the UK and

was a key strategic aim of the CSG following the strategy meeting. This proposal has been

developed in consultation with BCRT, the key funder, and has recently been funded and

subsequently adopted in the near future. This proposal also supports a large translational

component, separately funded through a large charitable donation. The ICONIC,

Chondrosarcoma and Chordoma studies have all benefitted from this new collaborative

strategy.

Develop studies where there were none, for osteosarcoma and chondrosarcoma

The ICONIC osteosarcoma study was part funded by BCRT to the sum of £ 449,631.79, with

separate funding achieved from the Tom Prince Trust for the translational element. The study

is being sponsored by the UCL CTU and should open in 2018.

The first portfolio study on chondrosarcoma is now open in four of the five primary bone

sarcoma centres. Does circulating DNA predict the grade and disease burden of

chondrosarcoma? A nationwide collaboration study received £69,963 funding from BCRT and

has already recruited 29/130 patients having only been open for a few months. Work

developing a successor study for this study will need to begin soon.

Promote national collaboration in the development and delivery of studies

The studies described above are both multicentre, national proposals which the Subgroup has

encouraged, with investigators and study delivery in more than one centre. The word

collaboration appears in the title of both ICONIC and the Chondrosarcoma study as this was a

major strategic aim of the Subgroup and CSG. Engagement from all the bone sarcoma centres

has been excellent thus far.

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Young Onset Soft tissue Subgroup (Chair, Professor Bernadette Brennan)

Open a first line study in Rhabdomyosarcoma across all ages and 2. Build in current

relapse studies in RMS using VIT as the backbone

These two strategic aims have progressed with the submission and successful funding by the

CRUK of FaR-RMS: A multiarm-multistage study for children and adults with localised and

metastatic Frontline and Relapsed Rhabdomyosarcoma (in set up).

Trial summary: The FaR-RMS Study is an overarching clinical trial that explores several aspects

of treatment for RMS, both for patients newly diagnosed with the disease and also at the time

of relapse. It is open to patients of all ages (children, TYA and adults) across Europe who are

newly diagnosed with RMS or in whom the disease recurs.

To develop an all age European study in specific soft tissue which occurs in paediatric, TYA

and adult age group e.g. Synovial Sarcoma, MPNST, leiomyosarcoma and liposarcoma

There is a trial in early development within Europe to examine the role of Olaratumab in

addition to ifosfamide and doxorubicin in high risk soft tissue sarcomas, which will lower the

traditional age limit of 18 to include TYA and paediatric subjects.

Build on the outcomes of other rare sarcomas from the NRSTS study to develop further

clinical trials, specifically Rhabdoid tumours at all sites and synovial sarcoma

This will be progressed by developing further clinical trials.

EURO RHABDOID 2018 (study in planning):

• Initial discussion re sponsorship and trial development with Birmingham Children’s Cancer

CTU

• Planned countries: UK, France, Spain, Netherlands, Sweden, Norway, Denmark, Belgium,

Ireland, Slovakia, Czech Republic and Italy.

• Internationally developed as part of the European Paediatric Soft Tissue Sarcoma Group

(EpSSG)

Title: A phase Ib/II study evaluating the addition of a new agent X in children and adolescents

with high risk malignant rhabdoid tumours (MRT) or atypical teratoid/rhabdoid tumours

(AT/RT) at diagnosis.

To embed biological studies, biomarkers and novel targets into clinical trial portfolio

This will be achieved in FaR-RMS as above and EpSSG NRSTS 2018 - a successor to EpSSG

NRSTS 2005 which will be a prospective cohort study with a biological question, which may be

useful for all the NRSTS subtypes.

Increase the TYA population in sarcoma studies

This will be achieved by extending the upper age range for study entry in all proposed studies

above

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4. Task groups/Working parties

Remit of Gynaecological Sarcomas Working Party

The aim of the Working Party is to gain a better understanding of the different treatments

gynae-sarcoma patients receive across the UK. The group wishes to produce guidelines for

every gynae-sarcoma patient to be seen by a sarcoma MDT from a gynae-sarcoma

questionnaire.

Progress to date

The Working Party has been working in close collaboration with the EORTC Soft tissue and

Bone Sarcoma Group. Due to the rarity of this group of tumours the majority of studies

require European and International collaboration. A trial is currently recruiting, which is part

of the International Rare Cancer Initiative (IRCI) in collaboration with the GOG and EORTC,

investigating the role of cabozantinib maintenance therapy in patients with uterine sarcoma

who have responded to first line chemotherapy. This is open and recruiting at 4 UK sites. The

group have developed a gynae-sarcoma questionnaire, in collaboration with Sarcoma UK, in

response to a patient query on the Sarcoma UK support line regarding routine hormone

testing on uterine Leiomyosarcoma. Collaboration is anticipated with NCRAS and the NCRAS

Gynae Expert Advisory Group. The group also suggested having a gynae sarcoma session at

the 2018 BSG meeting, with the bonus that it would attract more pathologists.

Remit of Lung Metastases Working Party

The main focus of this Working Party is to deliver a trial on metastatic sarcoma, the SARC-MET

programme.

Progress to date

The Lung Metastases Working Party consists of 3 adult oncologists, a statistician, 2

scientists/epidemiologists with expertise in quality of life outcomes in cancer, a consumer

representative, representation from the Supportive & Palliative Care CSG and are currently

trying to recruit a health economist.

The trial is being supported by Birmingham Clinical Trial Unit. The trial would aim to determine

whether outcomes from metastatic bone and soft tissue sarcoma can be improved by

intervention trials of PROM intervention + Standard Oncological Care (SOC) versus SOC alone,

with sub studies in minimally invasive techniques vs open surgery techniques to treat

pulmonary metastases and timing of systemic therapy. There would also be an overarching

assessment of quality of life, cost and geography for metastatic sarcoma care to incorporate

into an economic cost analysis of metastatic bone and soft tissue sarcoma. The protocol has

been written, discussed at the main CSG meeting and the trial is being aimed towards NIHR

funding, however, a smaller feasibility study is planned before major funding is sought. This

working party has worked very well and collaboratively with other CSGs to develop this

important trial.

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5. Funding applications in last year

Table 2 Funding submissions in the reporting year

Cancer Research UK Clinical Research Committee (CRUK CRC)

Study Application type CI Outcome Level of CSG input

May 2017

None

November 2017

Exploiting circulating miRNAs to predict response

and toxicity in patients with Ewing’s sarcoma

Biomarker

Project Award

(Full Application)

Professor Susan

Burchill

Not Supported

Validation of biomarkers for Malignant Peripheral

Nerve Sheath Tumour (MPNST) and atypical

meningiomas

Biomarker

Project Award

(Full Application)

Professor Dr

Clemens

Hanemann

Not Supported

Other committees

Study Committee &

application type

CI Outcome Level of CSG input

CRUK/17/011 FaR-RMS: A multiarm-multistage

study for children and adults with localised and

metastatic Frontline and Relapsed

RhabdoMyoSarcoma. January 2018 - December

2028

CRUK

Dr Meriel Jenney Successful • Developed within YOSS

Subgroup

• Sum: £2,330,159.53

• The approval letter was

received in November

2017 and the first

patient must be entered

within 12 months of this

date

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• The grant was activated

on 1st February 2018

ICONIC: Improving outcome through Collaboration

in OsteosarComa

BCRT Dr Sandra Strauss Successful • Developed within Bone

Subgroup

• Sponsor: UCL Cancer

Trials Centre (UCL CTC)

• Sum: £ 449,631.79

• Funded after Interview:

8/3/2017

Molecular characterisation of primary uterine

leiomyosarcoma and preclinical investigation of

response to non-genotoxic activators of p53 via

the MDM2/p53/PPM1D signalling network

Sarcoma UK Professor John

Lunec

Successful

Towards the production of high potency peptide

therapeutics for the treatment of Kaposi’s

sarcoma

Sarcoma UK Dr Tracey Barrett Successful

Investigating the role and mechanisms of small

non-coding RNAs in chondrosarcoma: A small RNA

sequencing approach.

Sarcoma UK Dr Mandy Peffers Successful

Linking cellular heterogeneity to therapeutic

response in rhabdomyosarcomas

Sarcoma UK Dr Zoe Walters Successful

Characterisation of the Role Of Sarcoma-

Associated Fibroblasts in Soft Tissue Sarcoma

Development

Sarcoma UK Dr Will English Successful

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Utilisation of Genomic mutational signatures in

sarcoma for clinical benefit

Sarcoma UK Dr Nischalan Pillay Successful

CIRCUS: A pilot study of CIRCUlating tumour cells

in patients with soft tissue Sarcoma

Sarcoma UK Dr Robin Young Successful

Trans-TITAN: Translational analysis of samples

from the TITAN (Tumoural Injection of T-VEC and

Isolated Limb Perfusion) study

Sarcoma UK Mr Andrew Hayes Successful

Circulating Tumour Cells as Predictors of Disease

Progression and Overall Survival in Dogs with

Naturally-occurring Osteosarcoma

Sarcoma UK Prof Matthew Allen Successful

Improving soft-tissue sarcoma diagnosis with non-

invasive procedures

Sarcoma UK Prof David

Gonzalez de

Castro

Successful

Exploring socio-demographic inequalities in the

diagnosis of sarcoma, with a particular focus on

deprivation

Sarcoma UK Dr Richard

McNally

Successful

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6. Consumer involvement

Michael Maguire

Michael Maguire is the only current consumer representative as Miss Ray Davies had to withdraw

from the CSG due to a career move abroad.

Michael continues to provide consumer involvement within CSG meetings and activities as well

as providing easy access to a wider pool of experienced consumers in the NCRI Consumer Forum.

With this availability of experience and knowledge to critique, question and add ideas to the

group, Michael continually supports a key aim of the CSG, to develop new clinical studies. We

look forward to a new consumer joining the CSG in the next round of recruitment to continue this

trend.

Michael has and will continue to provide involvement input to the proposal of the VMPRASS study

proposal that Dr Paul Huang and Dr Robin Jones are leading on. The proposal was pitched to a

group of consumers at the NCRI Consumer Forum’s Dragons Den session in March 2018 and

was presented at the Sarcoma CSG meeting in May 2018. Michael continues to support the

development of a study in the development of follow-up and will continue to work with Mr

Jonathan Gregory and Dr Paula Wilson in progressing a study in follow-up.

7. Priorities and challenges for the forthcoming year

Priority 1

Formation of the Soft Tissue Sarcoma (STS) Subgroup to co-ordinate and enhance the

development of further studies in STS and champion the SARC-MET study to successful

funding.

Priority 2

To successfully oversee the launch of ICONIC study following recent funding to maximise the

potential number of centres open and patient recruitment.

Priority 3

To successfully oversee the launch of FaR-RMS. Following the successful funding by the CRUK

of FaR-RMS: A multiarm-multistage study for children and adults with localised and metastatic

Frontline and Relapsed Rhabdomyosarcoma the trial is in set up and will require significant

work to open it in multiple centres

Challenge 1

To set up the STS Subgroup and develop new sarcoma trials to complement current trials on

the portfolio.

Challenge 2

To develop SARC-MET trial and obtain suitable funding.

Challenge 3

To develop surgical questions and embed within new trials or develop standalone trials.

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8. Appendices

Appendix 1 - Membership of main CSG and subgroups

Appendix 2 – CSG and Subgroup strategies

A – Main CSG Strategy

B – Bone Tumour Subgroup Strategy

C – Young Onset Soft-tissue Sarcoma Subgroup Strategy

Appendix 3 - Portfolio Maps

Appendix 4 – Top 5 publications in reporting year

Appendix 5 – Recruitment to the NIHR portfolio in the reporting year

Professor Lee Jeys (Sarcoma CSG Chair)

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Appendix 1

Membership of the Sarcoma CSG

Name Specialism Location

Dr Laura Forker* Clinical Oncologist Manchester

Dr Aisha Miah Clinical Oncologist London

Dr Beatrice Seddon Clinical Oncologist London

Dr Paula Wilson Clinical Oncologist Bristol

Dr Alexander Lee* Clinical Research Fellow London

Mr Michael Maguire Consumer London

Mr Roger Wilson Consumer Shropshire

Dr Charlotte Benson Medical Oncologist London

Dr Louise Carter Medical Oncologist Manchester

Dr Sarah Pratap Medical Oncologist Oxford

Dr Sandra Strauss Medical Oncologist London

Professor Luc Bidaut Medical Physicist Lincoln

Mrs Helen Stradling Nurse Oxford

Dr Bernadette Brennan Paediatric Oncologist Manchester

Dr Angela Edgar Paediatric Oncologist Edinburgh

Dr Malee Fernando Pathologist Sheffield

Dr Rajesh Botchu Radiologist Radiologist

Professor Sue Burchill Radiologist Radiologist

Ms Sarah McDonald Sarcoma UK Representative London

Mrs Sharon Forsyth Senior Trials Coordinator London

Mr Piers Gaunt Statistician Birmingham

Mr Craig Gerrand Surgeon Newcastle

Mr Jonathan Gregory Surgeon Manchester

Professor Lee Jeys (Chair) Surgeon Birmingham

* denotes trainee member

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Membership of the Subgroups

Bone Tumour Subgroup

Name Specialism Location

Dr Fiona Cowie Clinical Oncologist Glasgow

Mrs Kelle Vernon Consumer Birmingham

Dr Sandra Strauss Medical Oncologist London

Professor Jeremy Whelan Medical Oncologist London

Dr Bruce Morland Paediatric Medical

Oncologist Birmingham

Dr Bernadette Brennan Paediatric Oncologist Manchester

Professor Donald Salter Pathologist Edinburgh

Professor Sue Burchill Radiologist Leeds

Mr Matthew Sydes Statistician London

Professor Keith Wheatley Statistician Birmingham

Mr Craig Gerrand (Chair) Surgeon Newcastle

Young Onset Soft tissue Sarcoma Subgroup

Name Specialism Location

Dr Henry Mandeville Clinical Oncologist London

Dr Aisha Miah Clinical Oncologist London

Dr Palma Dileo Medical Oncologist London

Professor Winette van der

Graaf

Medical Oncologist London

Dr Julia Chisholm Paediatric Medical

Oncologist

London

Dr Maddi Adams** Paediatric Oncologist Cardiff

Dr Bernadette Brennan (Chair) Paediatric Oncologist Manchester

Dr Merial Jenney Paediatric Oncologist Cardiff

Dr Jennifer Turnbull** Paediatric Registrar Oxford

Dr Anna Kelsey Pathologist Manchester

Dr Kieran McHugh Radiologist London

Mr Ross Craigie Surgeon Manchester

Mr Tim Rogers Surgeon Bristol

Dr Janet Shipley Translational Scientist London

* denotes trainee member

**denotes non-core member

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Appendix 2

CSG & Subgroup Strategies

A – Main CSG Strategy

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B – Bone Tumour Subgroup Strategy

Strategic priorities

1. To develop and deliver a study in chondrosarcoma.

2. To develop and deliver a study in osteosarcoma.

3. To support the delivery of studies in Ewings sarcoma.

4. To promote national collaboration in the development and delivery of studies.

Progress against priorities

1. A study of IDH1/2 mutations in the serum of chondrosarcoma patients has been funded

and will open this year.

2. A proposal for funding of a large umbrella study in osteosarcoma is being developed with

a view to a submission to BCRT later this year.

3. Recruitment to EE2012, REECUR and related studies has been supported by the

Subgroup. Adoption to the portfolio has increased the opportunity to recruit to the

GenoEwings and Predict studies.

4. The Subgroup is able to engage with a larger number of members increasing its national

reach thanks to BCRT funding. All studies under development are either multicentre or

will become so, including the chondrosarcoma study, the osteosarcoma study in

development and the Sarcoma PROMS study.

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C – Young Onset Soft-tissue Sarcoma Subgroup Strategy

The group recognises the continuing challenges:

• To increase participation of the TYA population in trials, indeed extending all our trials and

research to the adult age group.

• The necessity for stable international consortia to develop trials where patient numbers in the

UK are small.

• Obtaining access to new agents from pharma companies for younger patients, and indeed in

sarcomas.

• Funding the parallel biological studies in international trials

Agreed strategic priorities for YOSS:

1. To open a first line study in Rhabdomyosarcoma across all ages in paediatric, TYA and adult

sites in UK and indeed European countries who are part of the EpSSG

2. To build on current relapse studies in RMS using VIT as backbone- this strategic aim is

incorporated into the FaR-RMS study

3. To develop an all age European study in specific soft tissue which occur in paediatric, TYA and

adult age group e.g. Synovial Sarcoma, MPNST, leiomyosarcoma and liposarcoma.

4. To build on the outcomes of other rare sarcomas from the NRSTS study to develop further

clinical trials specifically Rhabdoid tumours at all anatomical sites.

5. To embed biological studies, biomarkers and novel targets into clinical trial portfolio

6. To open a prospective cohort study with a biological question that may be useful for all the

NRSTS subtypes in particular those which mainly occur in the paediatric age group.

7. To increase the TYA population in sarcoma studies.

Planned implementation:

1. FaR-RMS: A multiarm-multistage study for children and adults with localised and metastatic

Frontline and Relapsed RhabdoMyoSarcoma new study proposal has been funded by CRUK and

will be opened by the end of 2018.

2. See above

3. To develop an all age European study in specific soft tissue sarcomas. There is a trial in early

development within Europe to examine the role of Olaratumab in addition to ifosfamide and

doxorubicin in high risk soft tissue sarcomas, which will lower the traditional age limit of 18 to

include TYA and paediatric subjects.

4. To build on the outcomes of other rare sarcomas from the NRSTS study to develop further

clinical trials (EURO RHABDOID 2017 study in planning).

5. To embed biological studies, biomarkers and novel targets into clinical trial portfolio. This will

be achieved in FaR-RMS and EpSSG NRSTS 2018

26

6. To open a prospective cohort study with a biological question that may be useful for all the

NRSTS subtypes. This will be achieved with EpSSG NRSTS 2018.

7. To increase the TYA population in sarcoma studies- this will be achieved by extending the

upper age range for study entry

27

Appendix 3

Portfolio maps

28

29

Appendix 4

Top 5 publications in the reporting year

Please note that the below is incomplete

Trial name & publication reference Impact of the trial CSG involvement in the trial

1. Survival is influenced by approaches to local

treatment of Ewing sarcoma within an

international randomised controlled trial:

analysis of EICESS-92. Whelan J et al, Clin

Sarcoma Res. 2018 Mar 30;8:6.

Unexpected differences in EFS and OS occurred between

two patient cohorts recruited within an international

randomised trial. Failure to select or deliver appropriate

local treatment modalities for Ewing's sarcoma may

compromise chances of cure. 5-year EFS rates were 43%

(95% CI 36-50%) and 57% (95% CI 52-62) in the CCLG

and GPOH patients, respectively; corresponding 5-year

OS rates were 52% (95% CI 45-59%) and 66% (95% CI

61-71). CCLG patients were less likely to have both

surgery and radiotherapy (18 vs. 59%), and more likely to

have a single local therapy modality compared to the

GPOH patients (72 vs. 35%). Forty-five percent of GPOH

patients had pre-operative radiotherapy compared to 3%

of CCLG patients. In the CCLG group local recurrence

(either with or without metastases) was the first event in

22% of patients compared with 7% in the GPOH group

Members of the CSG were

involved in the development of

the EICESS-92 study and wrote

this paper from the data.

2. Surgery alone is sufficient therapy for children

and adolescents with low-risk synovial

sarcoma: a joint analysis from the European

paediatric Soft tissue sarcoma Study Group

It confirms in large numbers that this should be the

standard therapy for these patients, and small tumours

do not need adjuvant chemotherapy

Members of the CSG were

involved in the development of

the EpSSG NRSTS study and

co- wrote this paper from the

data.

30

and the Children’s Oncology Group. Ferrari A

et al, Eur J Cancer 2017 Jun;78:1-6.

3. Alveolar soft part sarcoma in children and

adolescents: The European Paediatric Soft

Tissue Sarcoma study group prospective trial

(EpSSG NRSTS 2005). Brennan B et al, Pediatr

Blood Cancer. 2018 Apr;65(4).

This report demonstrates the ability to run prospective

pediatric studies in NRSTS in multiple European

countries, despite the small numbers of ASPS patients.

We can conclude that for the majority with small

resected tumors, there were few events and no deaths.

Members of the CSG were

involved in the development of

the EpSSG NRSTS study and

co- wrote this paper from the

data.

31

Appendix 5

Recruitment to the NIHR portfolio in the reporting year

In the Sarcoma CSG portfolio, 6 trials closed to recruitment and 11 opened.

Summary of patient recruitment by Interventional/Non-interventional

Year All participants Cancer patients only % of cancer patients relative

to incidence

Non-

interventional

Interventional Non-

interventional

Interventional Non-

interventional

Interventional

2013/2014 43 195 25 195 - -

2014/2015 145 115 145 115 - -

2015/2016 58 130 58 130 - -

2016/2017 208 206 184 206 - -

2017/2018 360 223 346 223 - -